Descartes frequently sets his views apart from those of his predecessors. In the opening section of the Passions of the Soul, a treatise on the Early Modern version of what are now commonly called emotions, he goes so far as to assert that he will write on his topic "as if no one had written on these matters before". Many elements of his philosophy have precedents in late Aristotelianism, the revived Stoicism of the 16th century, or in earlier philosophers like St. Augustine. In his natural philosophy, he differs from the Schools on two major points: First, he rejects the analysis of corporeal substance into matter and form; second, he rejects any appeal to ends—divine or natural—in explaining natural phenomena.[3] In his theology, he insists on the absolute freedom of God’s act of creation.

I entirely abandoned the study of letters. Resolving to seek no knowledge other than that of which could be found in myself or else in the great book of the world, I spent the rest of my youth traveling, visiting courts and armies, mixing with people of diverse temperaments and ranks, gathering various experiences, testing myself in the situations which fortune offered me, and at all times reflecting upon whatever came my way so as to derive some profit from it. (Descartes, Discourse on the Method)

In 1622 he returned to France, and during the next few years spent time in Paris and other parts of Europe. He arrived in La Haye in 1623, selling all of his property, investing this remuneration in bonds which provided Descartes with a comfortable income for the rest of his life. Descartes was present at the siege of La Rochelle by Cardinal Richelieu in 1627.

Despite these frequent moves he wrote all his major work during his 20 plus years in the Netherlands, where he managed to revolutionize mathematics and philosophy. In 1633, Galileo was condemned by the Roman Catholic Church, and Descartes abandoned plans to publish Treatise on the World, his work of the previous four years. "Discourse on the Method" was published in 1637. In it an early attempt at explaining reflexes mechanistically is made. Descartes also lays out four rules of thought, meant to ensure that our knowledge rests upon a firm foundation.

René Descartes died on 11 February 1650 in Stockholm, Sweden, where he had been invited as a teacher for Queen Christina of Sweden. The cause of death was said to be pneumonia — accustomed to working in bed until noon, he may have suffered a detrimental effect on his health due to Christina's demands for early morning study (the lack of sleep could have severely compromised his immune system). Others believe that Descartes may have contracted pneumonia as a result of nursing a French ambassador, Dejion A. Nopeleen, ill with the aforementioned disease, back to health.[8]